A Phase II Clinical Trial Evaluating the Efficacy and Safety of GDC-0449 in Children With Recurrent or Refractory Medulloblastoma
I. Estimate the efficacy of GDC-0449 treatment for pediatric patients with recurrent or
refractory medulloblastoma, as measured by the sustained objective response rates for
patients without (stratum A) and with (stratum B) evidence of activation of Hedgehog (Hh)
signaling pathway in their tumors.
II. Characterize the pharmacokinetics (plasma) of GDC-0449 in children/adolescents with
I. Document and describe toxicities associated with GDC-0449 administered on a daily
II. Estimate the duration of objective response and progression-free survival (PFS).
III. Document pathologic and genomic methods to identify medulloblastomas with activation of
the Hh signaling pathway.
IV. Characterize the pharmacokinetics (cerebrospinal fluid) of GDC-0449 in
children/adolescents with refractory medulloblastoma.
OUTLINE: This is a multicenter study. Patients are stratified according to evidence of
activation of Hedgehog signaling pathway in their tumors (without vs with vs unknown).
Patients receive oral Hedgehog antagonist GDC-0449 once daily on days 1-28. Treatment
repeats every 28 days for up to 26 courses in the absence of disease progression or
Plasma and cerebrospinal fluid samples are collected periodically for pharmacokinetic and
other correlative studies.
After completion of study treatment, patients are followed up for up to 12 months.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Objective response rates (partial and complete response)
Simon two-staged MinMax designs will be used to assess the rates of best objective response prior to progression.
Up to 12 months
Pediatric Brain Tumor Consortium
United States: Food and Drug Administration
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|Stanford University||Stanford, California 94305|
|Pediatric Brain Tumor Consortium||Memphis, Tennessee 38105|